Distinctive neurochemical patterns associated with specific abnormalities in catecholamine biosynthesis, storage, release, disposition, and metabolism were described in several genetic or acquired diseases. Children with Menkes' disease, a disorder of copper metabolism, had evidence for decreased activity of dopamine-beta-hydroxylase (DBH), with DOPA:dihydroxyphenylglycol (DHPG) ratios invariably increased, enabling in utero diagnosis and early treatment. Dihydropteridine reductase (DHPR) deficiency causes an atypical form of phenylketonuria. Our finding of low but detectable levels of DOPA and other catechols in a patient with absent DHPR implies that in humans, DHPR is not absolutely required for catecholamine synthesis. Patients with familial dysautonomia (FD) had a characteristic, distinct neurochemical pheno-type, with high ratios of plasma DOPA:DHPG and normal plasma NE, DA, and dihydroxyphenylacetic acid (DOPAC) levels. The phenotype predicts a mutation that produces arrested differentiation of peripheral catecholaminergic systems. Patients with inherited deficiency of MAO-A had very low levels of DHPG, whereas patients with deficiency of MAO-B did not, providing a means to distinguish neurochemically deficiencies of the two isoforms of the enzyme. Plasma levels of free (unconjugated) metanephrines diagnosed pheochromocytoma better than did any other neurochemical test. Several studies assessed catecholaminergic neurochemical correlates of physiological and pathophysiologic states or drug treatments. A study combining direct sympathetic nerve recording with neurochemical methods provided the first evidence for glucocorticoid-induced sympathoinhibition in humans, indicating a potentially important interaction between two of the body's main stress effector systems. Prolonged head-down bed rest was used as a model of chronic exposure to zero-gravity during space flight. Neurochemical findings indicated that chronic sympathoinhibition accompanies the orthostatic intolerance that always occurs during re- exposure to the earth's gravity. A characteristic neurocirculatory pattern was found to precede neurocardiogenic syncope, with blunted increases in forearm NE spillover during nonhypotensive LBNP and augmented plasma epinephrine (EPI) responses. In a patient with the Shy- Drager syndrome and multiple myeloma, in vitro testing supported an autoimmune causal mechanism for the disease. Results of a collaborative study of clozapine indicated that this novel neuroleptic affects several aspects of peripheral noradrenergic function. We obtained evidence for functional stimulatory beta-adrenoceptors on sympathetic terminals in the human forearm, without evidence for functional stimulatory receptors for angiotensin II. In humans, the main identified modulator of transmitter release from sympathetic nerves appeared to be inhibitory, mediated by alpha2-adrenoceptors.